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The O-Linked Glycome and Blood Group Antigens ABO on Mucin-Type Glycoproteins in Mucinous and Serous Epithelial Ovarian Tumors

Artikel i vetenskaplig tidskrift
Författare Varvara Vitiazeva
Jayesh Kattla
Sarah A. Flowers
Sara K. Lindén
Pushpa Premaratne
Birgitta Weijdegård
Karin Sundfeldt
Niclas G. Karlsson
Publicerad i Plos One
Volym 10
Nummer/häfte 6
Sidor Article Number: e0130197
ISSN 1932-6203
Publiceringsår 2015
Publicerad vid Institutionen för biomedicin
Institutionen för biomedicin, avdelningen för medicinsk kemi och cellbiologi
Institutionen för kliniska vetenskaper, Avdelningen för obstetrik och gynekologi
Sidor Article Number: e0130197
Språk en
Länkar dx.doi.org/10.1371/journal.pone.013...
Ämnesord CARBOHYDRATE ANTIGENS, BIOMARKERS HE-4, CANCER, EXPRESSION, CARCINOMAS, PROTEINS, GLYCOSYLATION, MASS, IDENTIFICATION, DIAGNOSIS, Multidisciplinary Sciences
Ämneskategorier Reproduktionsmedicin och gynekologi

Sammanfattning

Background Mucins are heavily O-glycosylated proteins where the glycosylation has been shown to play an important role in cancer. Normal epithelial ovarian cells do not express secreted mucins, but their abnormal expression has previously been described in epithelial ovarian cancer and may relate to tumor formation and progression. The cyst fluids were shown to be a rich source for acidic glycoproteins. The study of these proteins can potentially lead to the identification of more effective biomarkers for ovarian cancer. In this study, we analyzed the expression of the MUC5AC and the O-glycosylation of acidic glycoproteins secreted into ovarian cyst fluids. The samples were obtained from patients with serous and mucinous ovarian tumors of different stages (benign, borderline, malignant) and grades. The O-linked oligosaccharides were released and analyzed by negative-ion graphitized carbon Liquid Chromatography (LC) coupled to Electrospray Ionization tandem Mass Spectrometry (ESI-MSn). The LC-ESI-MSn of the oligosaccharides from ovarian cyst fluids displayed differences in expression of fucose containing structures such as blood group ABO antigens and Lewis-type epitopes. The obtained data showed that serous and mucinous benign adenomas, mucinous low malignant potential carcinomas (LMPs, borderline) and mucinous low-grade carcinomas have a high level of blood groups and Lewis type epitopes. In contrast, this type of fucosylated structures were low abundant in the high-grade mucinous carcinomas or in serous carcinomas. In addition, the ovarian tumors that showed a high level of expression of blood group antigens also revealed a strong reactivity towards the MUC5AC antibody. To visualize the differences between serous and mucinous ovarian tumors based on the O-glycosylation, a hierarchical cluster analysis was performed using mass spectrometry average compositions (MSAC). Mucinous benign and LMPs along with mucinous low-grade carcinomas appear to be different from serous and high-grade mucinous carcinomas based on their O-glycan profiles.

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